Sustained or controlled release products for oral administration are known and widely used. Hydroxypropyl methylcellulose has been used in such products. It is believed that hydroxypropyl methylcellulose in such tablets partially hydrates on the tablet surface to form a gel layer. The rate of hydration and gelling of the hydroxypropyl methylcellulose tablet surface affects the drug release from the tablet and contributes significantly to the sustained release aspect of such products.
However, it has been difficult to formulate controlled release tablets of soluble medicaments and hydroxypropyl methylcellulose. First, it has been difficult to achieve the desired dissolution profiles or to control the rate of release of soluble to freely soluble medicaments. This may be due to leaching of the medicament from the tablet before hydration and gelling of the hydroxypropyl methylcellulose occurs. Second, known tableting techniques such as direct compression and granulation may fail when a high proportion of soluble medicament is required regardless of its degree of solubility.
Bead coating technology can be used to form sustained release products. These products typically comprise hard gelatin capsules containing coated beads of medicament. Soluble medicaments are available in controlled release capsules of this type. However, tablets have certain advantages over capsules and these advantages are lost with the use of capsules for sustained release of soluble therapeutic agents.
Tablets have several advantages over capsules. For some drugs, it is recommended that the patient begin taking a smaller dose and gradually over time increase the dose to the desired level. This can help avoid undesirable side effects. Tablets can be preferable to capsules in this regard because a scored tablet easily can be broken to form a smaller dose.
In addition, tableting processes such as wet granulation are generally simpler and less expensive than bead coating and capsule formation. Further, tablets can be safer to use because they may be less subject to tampering.
Accordingly, a need exists for a controlled release product of more soluble medicaments, combining the advantages of hydroxypropyl methylcellulose in sustaining and controlling the release rate, the relative ease and low cost of wet granulation, and the other advantages of the tablet form over capsules.